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O00327 (BMAL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aryl hydrocarbon receptor nuclear translocator-like protein 1
Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP3
Brain and muscle ARNT-like 1
Class E basic helix-loop-helix protein 5
Short name=bHLHe5
Member of PAS protein 3
PAS domain-containing protein 3
bHLH-PAS protein JAP3
Gene names
Name:ARNTL
Synonyms:BHLHE5, BMAL1, MOP3, PASD3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length626 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ARNTL-CLOCK heterodimers activate E-box element (3'-CACGTG-5') transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER, and also by CRY proteins By similarity.

Subunit structure

Interacts with CRY2 By similarity. Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Interacts with HSP90; with AHR in vitro, but not in vivo. Part of a nuclear complex which also includes GNB2L1/RACK1 and PRKCA; GNB2L1 and PRKCA are recruited to the complex in a circadian manner. Ref.2 Ref.9

Subcellular location

Nucleus By similarity.

Tissue specificity

Highly expressed in the adult brain, skeletal muscle and heart.

Post-translational modification

Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression By similarity.

Phosphorylated upon dimerization with CLOCK By similarity.

Sumoylated on Lys-259 upon dimerization with CLOCK By similarity.

Miscellaneous

CLOCK-ARNTL double mutations within the PAS domains result in syngernistic desensitization to high levels of CRY on repression of CLOCK-ARNTL transcriptional activity of PER1 and, disrupt circadian rhythmicity.

Sequence similarities

Contains 1 basic helix-loop-helix (bHLH) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform BMAL1B (identifier: O00327-2)

Also known as: JAP3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform BMAL1A (identifier: O00327-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: MADQRMDISSTISDFMSPGPTDLLSSSLGTSGVDCNRKRKGSSTDYQ → MINI
Isoform BMAL1C (identifier: O00327-3)

The sequence of this isoform differs from the canonical sequence as follows:
     224-224: T → R
     225-626: Missing.
Isoform BMAL1D (identifier: O00327-4)

The sequence of this isoform differs from the canonical sequence as follows:
     274-391: Missing.
Isoform BMAL1E (identifier: O00327-5)

The sequence of this isoform differs from the canonical sequence as follows:
     278-301: SFCTIHSTGYLKSWPPTKMGLDED → AFCTIHSTGYFGIFTTRTSRHIVL
     302-626: Missing.
Isoform BMAL1F (identifier: O00327-6)

The sequence of this isoform differs from the canonical sequence as follows:
     443-526: ANVLEGGDPT...CGSSPLNITS → SRVDTGHLGQ...QGEPGLGQEK
     527-626: Missing.
Isoform MOP3 (identifier: O00327-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MADQRMDISS...MDTDKDDPHG → MSKEAVSLWA...CFYLLLFPPP
Isoform 8 (identifier: O00327-8)

The sequence of this isoform differs from the canonical sequence as follows:
     274-274: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 626626Aryl hydrocarbon receptor nuclear translocator-like protein 1
PRO_0000127156

Regions

Domain86 – 12641Helix-loop-helix motif
Domain143 – 21573PAS 1
Domain326 – 39671PAS 2
Domain401 – 44444PAC
DNA binding73 – 8513Basic motif

Amino acid modifications

Modified residue5381N6-acetyllysine By similarity
Cross-link259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence1 – 5959MADQR…DDPHG → MSKEAVSLWALTVSLQPPVP LCVCREMTGSGRRKQQCVTL PFISRELCFYLLLFPPP in isoform MOP3.
VSP_002095
Alternative sequence1 – 4747MADQR…STDYQ → MINI in isoform BMAL1A.
VSP_002094
Alternative sequence2241T → R in isoform BMAL1C.
VSP_002096
Alternative sequence225 – 626402Missing in isoform BMAL1C.
VSP_002097
Alternative sequence274 – 391118Missing in isoform BMAL1D.
VSP_002098
Alternative sequence2741Missing in isoform 8.
VSP_035457
Alternative sequence278 – 30124SFCTI…GLDED → AFCTIHSTGYFGIFTTRTSR HIVL in isoform BMAL1E.
VSP_002099
Alternative sequence302 – 626325Missing in isoform BMAL1E.
VSP_002100
Alternative sequence443 – 52684ANVLE…LNITS → SRVDTGHLGQVERCTVLSRP NSRFLIAGMFTEPTSWKAGT QPSHSSQHPPTAWTACCPLE KVAQRGPTPLFQGFQGEPGL GQEK in isoform BMAL1F.
VSP_002101
Alternative sequence527 – 626100Missing in isoform BMAL1F.
VSP_002102

Experimental info

Mutagenesis91S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL. Ref.10
Mutagenesis91S → F: 2-2.5-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. Ref.10
Mutagenesis101S → A or E: Enhanced PER1 reporter activity by CLOCK-ARNTL. Ref.10
Mutagenesis101S → L: 2-2.5-fold increase in CLOCK-ARNTL transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1. Ref.10
Mutagenesis6111A → S or T: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL transcriptional activity in the absence of CRY1; when associated with E-407. Ref.10
Mutagenesis6121G → E: Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-ARNTL transcriptional activity in the absence of CRY1. Ref.10
Sequence conflict691R → G in AAC51213. Ref.2
Sequence conflict1231K → R in BAA19935. Ref.1
Sequence conflict1731S → P in BAA19939. Ref.1
Sequence conflict2591K → N in BAA19938. Ref.1
Sequence conflict2641D → N in BAA19938. Ref.1
Sequence conflict4181S → N in BAA19937. Ref.1
Sequence conflict513 – 5142SP → LR in AAC51213. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform BMAL1B (JAP3) [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 820F0E07DC6265A6

FASTA62668,762
        10         20         30         40         50         60 
MADQRMDISS TISDFMSPGP TDLLSSSLGT SGVDCNRKRK GSSTDYQESM DTDKDDPHGR 

        70         80         90        100        110        120 
LEYTEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP TCNAMSRKLD KLTVLRMAVQ 

       130        140        150        160        170        180 
HMKTLRGATN PYTEANYKPT FLSDDELKHL ILRAADGFLF VVGCDRGKIL FVSESVFKIL 

       190        200        210        220        230        240 
NYSQNDLIGQ SLFDYLHPKD IAKVKEQLSS SDTAPRERLI DAKTGLPVKT DITPGPSRLC 

       250        260        270        280        290        300 
SGARRSFFCR MKCNRPSVKV EDKDFPSTCS KKKADRKSFC TIHSTGYLKS WPPTKMGLDE 

       310        320        330        340        350        360 
DNEPDNEGCN LSCLVAIGRL HSHVVPQPVN GEIRVKSMEY VSRHAIDGKF VFVDQRATAI 

       370        380        390        400        410        420 
LAYLPQELLG TSCYEYFHQD DIGHLAECHR QVLQTREKIT TNCYKFKIKD GSFITLRSRW 

       430        440        450        460        470        480 
FSFMNPWTKE VEYIVSTNTV VLANVLEGGD PTFPQLTASP HSMDSMLPSG EGGPKRTHPT 

       490        500        510        520        530        540 
VPGIPGGTRA GAGKIGRMIA EEIMEIHRIR GSSPSSCGSS PLNITSTPPP DASSPGGKKI 

       550        560        570        580        590        600 
LNGGTPDIPS SGLLSGQAQE NPGYPYSDSS SILGENPHIG IDMIDNDQGS SSPSNDEAAM 

       610        620 
AVIMSLLEAD AGLGGPVDFS DLPWPL

« Hide

Isoform BMAL1A [UniParc].

Checksum: 2AA8E7EEB4A71119
Show »

FASTA58364,207
Isoform BMAL1C [UniParc].

Checksum: 0A0580AEDC5A45A0
Show »

FASTA22425,353
Isoform BMAL1D [UniParc].

Checksum: 5FAB2403FD8AAB32
Show »

FASTA50855,462
Isoform BMAL1E [UniParc].

Checksum: EC942D8A9C9219B3
Show »

FASTA30133,922
Isoform BMAL1F [UniParc].

Checksum: ED01AF63A26CE4E0
Show »

FASTA52659,242
Isoform MOP3 [UniParc].

Checksum: 7A3FD8FAE5E496D7
Show »

FASTA62468,828
Isoform 8 [UniParc].

Checksum: 3F3F7D5688A6FFE2
Show »

FASTA62568,691

References

« Hide 'large scale' references
[1]"cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage."
Ikeda M., Nomura M.
Biochem. Biophys. Res. Commun. 233:258-264(1997) [PubMed: 9144434] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING (ISOFORMS BMAL1A; BMAL1B; BMAL1C; BMAL1D; BMAL1E AND BMAL1F).
Tissue: Brain.
[2]"Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway."
Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z., Pray-Grant M., Perdew G.H., Bradfield C.A.
J. Biol. Chem. 272:8581-8593(1997) [PubMed: 9079689] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MOP3), INTERACTION WITH HSP90 AND AHR.
Tissue: Fetal brain.
[3]"JAP3: a novel ARNT-like bHLH-PAS protein."
Tian H., Russell D.W., McKnight S.L.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BMAL1B).
[4]"The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors."
Hogenesch J.B., Gu Y.Z., Jain S., Bradfield C.A.
Proc. Natl. Acad. Sci. U.S.A. 95:5474-5479(1998) [PubMed: 9576906] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BMAL1B).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BMAL1B).
[6]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed: 16554811] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 8 AND BMAL1A).
Tissue: Brain and Skin.
[9]"Role of the CLOCK protein in the mammalian circadian mechanism."
Gekakis N., Staknis D., Nguyen H.B., Davis F.C., Wilsbacher L.D., King D.P., Takahashi J.S., Weitz C.J.
Science 280:1564-1569(1998) [PubMed: 9616112] [Abstract]
Cited for: INTERACTION WITH CLOCK.
[10]"Feedback repression is required for mammalian circadian clock function."
Sato T.K., Yamada R.G., Ukai H., Baggs J.E., Miraglia L.J., Kobayashi T.J., Welsh D.K., Kay S.A., Ueda H.R., Hogenesch J.B.
Nat. Genet. 38:312-319(2006) [PubMed: 16474406] [Abstract]
Cited for: MUTAGENESIS OF SER-9; SER-10; ALA-611 AND GLY-612.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		D89722 mRNA. Translation: BAA19968.1.
AB000812 mRNA. Translation: BAA19935.1.
AB000813 Genomic DNA. Translation: BAA19936.1.
AB000814 mRNA. Translation: BAA19937.1.
AB000815 mRNA. Translation: BAA19938.1.
AB000816 mRNA. Translation: BAA19939.1.
U51627 mRNA. Translation: AAC51213.1.
U60415 mRNA. Translation: AAB37248.1.
AF044288 mRNA. Translation: AAC24353.1.
AK291510 mRNA. Translation: BAF84199.1.
AC022878 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68504.1.
CH471064 Genomic DNA. Translation: EAW68511.1.
CH471064 Genomic DNA. Translation: EAW68513.1.
CH471064 Genomic DNA. Translation: EAW68510.1.
BC016674 mRNA. Translation: AAH16674.1.
BC031214 mRNA. Translation: AAH31214.1.
BC041129 mRNA. Translation: AAH41129.2.
IPIIPI00217732.
IPI00217734.
IPI00217735.
IPI00217736.
IPI00412162.
IPI00413132.
IPI00783543.
IPI00910251.
PIRJC5405.
JC5407.
PC4288.
PC4289.
RefSeqNP_001025443.1. NM_001030272.1.
NP_001025444.1. NM_001030273.1.
NP_001169.3. NM_001178.4.
UniGeneHs.65734.

3D structure databases

ProteinModelPortalO00327.
SMRO00327. Positions 71-129, 156-209, 330-444.
ModBaseSearch...

Protein-protein interaction databases

IntActO00327. 2 interactions.
STRINGO00327.

PTM databases

PhosphoSiteO00327.

Proteomic databases

PRIDEO00327.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000403290; ENSP00000384517; ENSG00000133794.
ENST00000403482; ENSP00000385897; ENSG00000133794.
GeneID406.
KEGGhsa:406.
UCSCuc001mkr.1. human.
uc001mkx.1. human.

Organism-specific databases

CTD406.
GeneCardsGC11P013299.
HGNCHGNC:701. ARNTL.
MIM602550. gene.
neXtProtNX_O00327.
GenAtlasSearch...

Phylogenomic databases

GeneTreeENSGT00570000078822.
HOVERGENHBG107503.
InParanoidO00327.
OMAGRLHSHV.
OrthoDBEOG4NS3B2.
PhylomeDBO00327.

Enzyme and pathway databases

Pathway_Interaction_DBcircadianpathway. Circadian rhythm pathway.
ReactomeREACT_24941. Circadian Clock.

Gene expression databases

ArrayExpressO00327.
BgeeO00327.
GenevestigatorO00327.
GermOnlineENSG00000133794. Homo sapiens.

Family and domain databases

InterProIPR011598. HLH_DNA-bd.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
Gene3DG3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KOK02296.
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. HLH_basic. 1 hit.
TIGRFAMsTIGR00229. Sensory_box. 1 hit.
PROSITEPS50888. HLH. 1 hit.
PS50113. PAC. False negative.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

SOURCESearch...

Entry information

Entry nameBMAL1_HUMAN
AccessionPrimary (citable) accession number: O00327
Secondary accession number(s): A8K645 expand/collapse secondary AC list , B5ME11, B7WPG7, D3DQW6, O00313, O00314, O00315, O00316, O00317, Q4G136, Q8IUT4, Q99631, Q99649
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: August 15, 2003
Last modified: January 25, 2012
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents